Influenza is a contagious acute respiratory disease caused by infection of the upper respiratory and gastrointestinal tract by influenza virus. The viral genome is made up of several negative sense single stranded RNA molecules. Several proteins are encoded by the viral genome. Neuraminidase (NA) is a viral surface glycoprotein that cleaves terminal sialic acid residues from carbohydrate moieties on the surfaces of infected cells, promoting the release of progeny viruses. Hemagglutinin (HA) is one of the major viral surface glycoproteins and involved in the binding of the virus to sialic acids on the surface of susceptible cells (Uiprasertkul M, et al. Emerg. Infect. Dis. 11, 1036-1041 (2005)). Influenza HA is a trimer on virus particles. Influenza HA is synthesized as HA0 by virus post-infection in cells that is cleaved by cellular proteases at the basic cleavage site into HA1 and HA2 mature forms, which is required for proper function of this surface protein and for viral life cycle. The M2 protein is an ion channel protein. The HA, NA, and M2 protein are present in the viral envelope which is derived from the host cell plasma membrane. A ribonucleoprotein complex comprises an RNA segment associated with nucleoprotein (NP) and three polymerases, PA, PB1, and PB2. The M1 protein is associated with both ribonucleoprotien and the envelope.
Annual epidemics of influenza occur when the antigenic properties of the viral surface protein hemagglutinin (HA) and neuraminidase (NA) are altered. The mechanism of altered antigenicity is twofold: antigenic shift, caused by genetic rearrangement between human and animal viruses after double infection of host cells, which can cause a pandemic; and antigenic drift, caused by small changes in the HA and NA proteins on the virus surface, which can cause influenza epidemics.
Recently a new H1N1 strain, designated 2009 A(H1N1) or simply “A(H1N1)” was identified (commonly referred to in the lay press as “swine flu”) and has become a pandemic. See, e.g., Garten et al., Science, 325:197-201 (2009).